Heterozygous tx mice have an increased sensitivity to copper loading: implications for Wilson\u27s Disease carriers

Wilson\u27s disease carriers constitute 1% of the human population. It is unknown whether Wilsons disease carriers are at increased susceptibility to copper overload when exposed to chronically high levels of ingested copper. This study investigated the effect of chronic excess copper in drinking water on the heterozygous form of the Wilson&rsquo;s disease mouse model &ndash; the toxic milk (tx) mouse. Mice were provided with drinking water containing 300 mg/l copper for 4&ndash;7, 8&ndash;11, 12&ndash;15 or 16&ndash;20 months. At the completion of the study liver, spleen, kidney and brain tissue were analyzed by atomic absorption spectroscopy to determine copper concentration. Plasma ceruloplasmin oxidase activity and liver histology were also assessed. Chronic copper loading resulted in significantly increased liver copper in both tx heterozygous and tx homozygous mice, while wild type mice were resistant to the effects of copper loading. Copper loading effects were greatest in tx homozygous mice, with increased extrahepatic copper deposition in spleen and kidney &ndash; an effect absent in heterozygote and wild type mice. Although liver histology in homozygous mice was markedly abnormal, no histological differences were noted between heterozygous and wild type mice with copper loading. Tx heterozygous mice have a reduced ability to excrete excess copper, indicating that half of the normal liver Atp7b copper transporter activity is insufficient to deal with large copper intakes. Our results suggest that Wilsons disease carriers in the human population may be at increased risk of copper loading if chronically exposed to elevated copper in food or drinking water.<br /

FLUXNET-CH4: A global, multi-ecosystem dataset and analysis

Methane (CH4) emissions from natural landscapes constitute roughly half of global CH4 contributions to the atmosphere, yet large uncertainties remain in the absolute magnitude and the seasonality of emission quantities and drivers. Eddy covariance (EC) measurements of CH4 flux are ideal for constraining ecosystem-scale CH4 emissions, including their seasonality, due to quasi-continuous and high temporal resolution of flux measurements, coincident measurements of carbon, water, and energy fluxes, lack of ecosystem disturbance, and increased availability of datasets over the last decade. Here, we 1) describe the newly published dataset, FLUXNET-CH4 Version 1.0, the first global dataset of CH4 EC measurements (available at https://fluxnet.org/data/fluxnet-ch4- community-product/). FLUXNET-CH4 includes half-hourly and daily gap-filled and non gap-filled aggregated CH4 fluxes and meteorological data from 79 sites globally: 42 freshwater wetlands, 6 brackish and saline wetlands, 7 formerly drained ecosystems, 7 rice paddy sites, 2 lakes, and 15 uplands. Then, we 2) evaluate FLUXNET-CH4 representativeness for freshwater wetland coverage globally, because the majority of sites in FLUXNET-CH4 Version 1.0 are freshwater wetlands and because freshwater wetlands are a substantial source of total atmospheric CH4 emissions; and 3) provide the first global estimates of the seasonal variability and seasonality predictors of freshwater wetland CH4 fluxes. Our representativeness analysis suggests that the freshwater wetland sites in the dataset cover global wetland bioclimatic attributes (encompassing energy, moisture, and vegetation-related parameters) in arctic, boreal, and temperate regions, but only sparsely cover humid tropical regions. Seasonality metrics of wetland CH4 emissions vary considerably across latitudinal bands. In freshwater wetlands (except those between 20° S to 20° N) the spring onset of elevated CH4 emissions starts three days earlier, and the CH4 emission season lasts 4 days longer, for each degree C increase in mean annual air temperature. On average, the onset of increasing CH4 emissions lags soil warming by one month, with very few sites experiencing increased CH4 emissions prior to the onset of soil warming. In contrast, roughly half of these sites experience the spring onset of rising CH4 emissions prior to the spring increase in gross primary productivity (GPP). The timing of peak summer CH4 emissions does not correlate with the timing for either peak summer temperature or peak GPP. Our results provide seasonality parameters for CH4 modeling, and highlight seasonality metrics that cannot be predicted by temperature or GPP (i.e., seasonality of CH4 peak). The FLUXNET-CH4 dataset provides an open-access resource for CH4 flux synthesis, has a range of applications, and is unique in that it includes coupled measurements of important CH4 drivers such as GPP and temperature. Although FLUXNET-CH4 could certainly be improved by adding more sites in tropical ecosystems and by increasing the number of site-years at existing sites, it is a powerful new resource for diagnosing and understanding the role of terrestrial ecosystems and climate drivers in the global CH4 cycle. All seasonality parameters are available at https://doi.org/10.5281/zenodo.4408468. Additionally, raw FLUXNET-CH4 data used to extract seasonality parameters can be downloaded from https://fluxnet.org/data/fluxnet-ch4-community-product/, and a complete list of the 79 individual site data DOIs is provided in Table 2 in the Data Availability section of this document.ISSN:1866-359